A Short History of Nutritional Science: Part 3 (1912-1944)
Time
                                           Notable People     Events leading to the discovery                  Discovery
  Year             Events
 1912      Vitamin Era              Casimir Funk                -   Anti-beriberi factor must be        “Vital Amines” = Vitamines
                                                                    an organic base and
                                                                    therefore contain amine
                                                                    group.
 1804                               Thomas Christie             -   Beriberi strive with            -     Difference of scurvy and
                                                                    stimulating & nourishing              beriberi is on chemical
                                                                    diet                                  combinations
 1830                               John Elliotson              -   Scurvy is a chemical disease    -     Remedy for scurvy is fresh
                                                                                                          food
 1842                               George Budd              Diseases caused by dietary
                                                             deficiencies
                                                                 1. Scurby
                                                                 2. Rickets
                                                                 3. Ulceration of the cornea
 1885-                              Gerrit Grijins           “A Short History of Nutritional        -     Organic nutrients are
 1912                                                        Science:Part 2”                              required in small amounts
                                                                                                          only.
           Rats and Mice fed                                 Purified diets – mixtures prepared     -     Find what combination of
           purified diets                                    from major nutrients                         supplements would restore
                                                             (protein,carbo & fat)                        purified diets to promoting
                                                                                                          good performance
           Various Literatures      Von Bunge                   -   The maintenance of small        -     Iron and Phosphorus should
           cited by E.V. McCollum                                   animals on purified diets             be part of organic
                                                                    had all failed.                       complexes in diet.
                                                                -   The failure of purified diets
                                                                    is on complexes being
                                                                    decomposed in the
                                                                    purification method
                                Cornelis Pekelharing   - Mice would not thrive on a         -   Mice were deficient in
                                                         simplified diet of casein,             nutrient that would supply
                                                         albumin, egg, rice flour and           them with whey
                                                         minerals.
                                Gowland Hopkins        - No animal can live upon the        -   Real error in diet is still
                                                           mixture of pure protein, fat         obscure/ unclear.
                                                           and carbohydrate.                -   He associates the
                                                                                                deficiencies of purified diet
                                                                                                with human disease
                                                                                                conditions.
                                Eijkman and Grijns     -   Feeding chicken with white       -   Chicken dies because of the
                                                           rice                                 deficiency in water-soluble
                                                                                                organic compound
1909                            Swiss opthalmologist   -   Appearance of eye lesions        -   The presence of
                                                           in rats fed in a purified diet       xerophthalmia &
                                                                                                keratomalacia that are
                                                                                                responsive to cod liver oil.
       McCollum’s First Trial   McCollum                                                    -   Animals needed to be
                                                                                                supplied with phosphorus
                                                                                                in the form of nucleic acids
                                                                                            -   The lack of palatability was
                                                                                                the limiting factor of
                                                                                                purified diets
                                                                                            -   Rats could manufacture
                                                                                                their own nucleic acid w/o
                                                                                                the need for phosphorus
                                                                                                and purines.
1911                            Osborne and Mendel     -   The desire to compare the        -   It leads to the study of
                                                           nutritional values of                vitamins.
                                                           isolated proteins in diet
                                                           with no other protein
                                                           source present.
1913   Factors “A” and “B”     McCollum          -   The use of phosphoprotein       -   Rats fed in a same amount
                                                     casein as purified protein          of organic contents will
                                                     source                              grow well in 8-14 weeks
                                                                                         and then lose weight after
                                                                                         some time.
                                                                                     -   Growth of the rats will
                                                                                         restart after having 1 g of
                                                                                         ether extract of egg.
1914                                                                                 -   Butterfat can stimulate the
                                                                                         growth of the rat.
                                                                                     -   Growth factor should be
                                                                                         non-saponifiable and fat
                                                                                         soluble.
                                                 -   Hopkins argued that the         -   McCollum and colleagues
                                                     growth of the rats from             agreed that rats need a fat-
                                                     their diet was because              soluble Factor A and water-
                                                     casein and lactose were not         soluble Factor B.
                                                     purified from a water-          -   The beginning of the
                                                     soluble growth factor.              scheme for identifying
                                                                                         vitamins by letters.
1917   Rickets and vitamin D   McCollum          -   Puppies fed with bread or       -   The discovery of another
                                                     oatmeal with whole milk             human disease, rickets.
                                                     would develop rickets.          -   The potent factors in
                                                                                         developing rickets are
                                                                                         inadequate fresh air and
                                                                                         exercise.
                               Edward Mellanby   -   Produced rickets in puppies     -   He could prevent the
                                                     by limiting their milk intake       occurrence of rickets with
                                                     and keeping them indoor             butter and cod liver oil and
                                                                                         exercise.
                                                                                     -   Oatmeal has a rachitic effect
                                                                                         on puppies.
1919                                                    -   The highlanders got              -   The discovery of using
                                                            offended by the remarks of           ultraviolet light to cure
                                                            Mellanby that oatmeal, as            rickets.
                                                            their traditional cereal food,
                                                            had a bad effects on dogs.
                             McCollum and colleagues    -   They use the rats as a model     -   Aerated cod liver oil with
                                                            having a diet which is               destroyed factor A value can
                                                            severely imbalance in the            still prevent ricket disease.
                                                            ratio of Calcium to
                                                            Phosphorus.
1931                                                                                         -   Coining the term “Vitamin
                                                                                                 D” as the activated material
                                                                                                 in the diet which cured
                                                                                                 ricket disease.
       Experimental scurvy   McCollum                   -   The rat models that he used      -   They concluded that each
                                                            no longer needed                     species has different
                                                            antiscorbutics (Vitamin C)           requirements in order to
                                                            to survive.                          survive therefore their
                                                                                                 results in their rat
                                                                                                 experiment will not be
                                                                                                 significant to other species.
1917                                                    -   They fed guinea pigs with        -   They debunk the findings
                                                            oats and milk resulting for          that scurvy is due to dietary
                                                            some of them to survive and          deficiency.
                                                            some to die in
                                                            autointoxication.
                             Harriette Chick and E.M.   -   They interpreted that cow’s      -   Scurvy appeared in
                             Hume                           milk wad only a low                  autoclaved milk that had
                                                            antiscorbutic acid, therefor         lost most of its vitamin C
                                                            guinea pigs needed at least          activity.
                                                            50 ml intake per day.
                                                        -   Commercial lime juice was        -   They conducted the first
                                                            not an effective                     bioassay for vitamin
                                                            antiscorbutic with less than         activity.
                                                                 1/10th of the activity of
                                                                 fresh lemon.
1928                            Albert Szent-Gyorgi          -   He used adrenal cortex            -   He unknowingly extracted
                                                                 tissues from slaughter                and isolate Vitamin C
                                                                 houses and rapid in vitro             despite its instability.
                                                                 assays.
1939                            Surgeon at Harvard Medical   -   He tried to have a diet           -   The dosing of ascorbic acid
                                School                           without Vitamin C but                 quickly cured the problems.
                                                                 supplement his body with
                                                                 other vitamins and discover
                                                                 after 26 weeks the
                                                                 development of
                                                                 hemorrhages on legs and
                                                                 unhealed wound on the
                                                                 back.
       Beriberi and Vitamin B   McCollum                     -   It was discovered that            -   The discovery of the second
                                                                 autoclaved yeast although             factors in the “antiberiberi
                                                                 lost its anti-neuritis activity       factor”, Vitamin B as
                                                                 still promoted the growth of          Vitamin B1 and B2
                                                                 beriberi in rats.
1926                            Dutch Scientists in Java     -   They used 10mg of crystals        -   They discovered the
                                                                 from rice polishing to cure           biologically active
                                                                 deficient pigeons and they            compound as Thiamin(e) as
                                                                 got a problem in                      the “vitamin containing
                                                                 determining the structure             sulfur”.
                                                                 of the crystals of the
                                                                 chloride salt.
                                Rudolph Peters               -   He discovered that deficient      -   They discovered that
                                                                 subjects maintained                   thiamin pyrophosphate
                                                                 unusually high levels of              served as a cofactor for the
                                                                 pyruvic or lactic acid in the         enzyme pyruvate
                                                                 blood after exercise.                 decarboxylase.
  -
1914   Pellagra in the United   Joseph Goldberger   -   He concluded that pellagra      -   He concluded that pellagra
       States                                           was not infectious.                 is caused by unbalanced
                                                    -   He received subcutaneous            diet of having abundant
                                                        injections of blood from            corn and cereals but
                                                        patients then had skin              without meat and dairy
                                                        eruptions rubbed into his           products.
                                                        nasal mucosa and then ate       -   Having failed to observe the
                                                        some of their excreta.              same symptoms of pellagra
                                                                                            in rats exposed with the
                                                                                            same diet, he concluded that
                                                                                            pellagra is caused by an
                                                                                            infectious agent.
1937                                                -   Dogs were given mixtures        -   Nicotinic acid was found to
                                                        with mostly cornmeal and            be extremely potent in
                                                        no meat or milk powder              curing black tongue thus it
                                                        developed a condition               was given with a name of
                                                        called “black tongue” which         “niacin”.
                                                        is quite similar to pellagra.
1935   Riboflavin                                   -   It was discovered that some     -   It was realized that B2 in
                                                        dogs with black tongue diet         autoclaved yeasts has a
                                                        had a prior condition of            complex factors and the first
                                                        yellow liver that could be          one to be investigated was
                                                        cured through riboflavin.           known to be riboflavin.
                                                    -   It was also found out that
                                                        pellagrins who have
                                                        cheilosis (lesions on the
                                                        mouth) responds quickly to
                                                        riboflavin.
1928   Folic Acid               Lucy Wills          -   She went to investigate         -   She found out that yeast and
                                                        more macrocytic anemia of           “Marmite” were highly
                                                        pregnant woman after                effective in curing
                                                        failing to associate them to        macrocytic anemia of
                                                        deficiency of Vitamin A & C.        pregnant women.
1937                                 -   They tried to feed rhesus       -   The rhesus monkeys
                                         monkey with Bombay diet             responded to Marmite and
                                         and found out that it               crude liver extracts but in
                                         induced macrocytic anemia           had no effect to patients
                                         and leucopenia.                     with pernicious anemia.
                                                                         -   They called the deficient
                                                                             factor as Vitamin M.
1944                                 -   Chicks fed with purified diet   -   They discovered that it
                                         with then known vitamins            could be prevented by
                                         still grew slowly and               giving them crystalline
                                         developed macrocytic                Vitamin BC.
                                         anemia.                         -   The same compound has
                                                                             been extracted from spinach
                                                                             and named as “folic acid”.
1937   Other B vitamins                                                  -   Pantothenic acid, B6 and
                                                                             biotin as water-soluble
                                                                             vitamins.
                                                                         -   Choline was recognized to
                                                                             be essential for poultry.
                          Fat Soluble Vitamins
       Vitamin A and                - The problem was to identify        -   Crystals of b-carotene were
       Carotene                         the Vitamin A which                  obtained from carrots and
                                        appeared to exist in:                found to be active.
                                        a. Highly colored form in        -   Carotene appeared to be a
                                            leaves and carrots               precursor of the final
                                        b. Colorless form in animal          vitamin.
                                            fat                          -   The vitamin is now named
                                    - It was found out that giving           as “retinol”
                                        carotenes to rats depleted
                                        of Vitamin A resulted from
                                        the reappearance of color
                                        reaction of the animal factor
                                        in extracts from their livers.
1922   Vitamins E and K        H.M. Evans and Katharine      They found out that purified       -    Lettuce was the first food to
                               Bishop                         diet with vitamin                       prevent this problem.
                                                              supplements that supported          - Cod liver oil unexpectedly
                                                              good growth in female rats              increase the problem.
                                                              nevertheless failed to          The active factor was named as
                                                              support normal                  Vitamin E and named as
                                                              reproduction.                   “tocopherol”.
1938                           Paul Karrer                   Vitamin E became a popular          - He synthesized Vitamin E by
                                                              treatment including                     condensing phytyl bromide
                                                              abortions, impotence and                with trimethyl hyroquinone.
                                                              muscular dystrophy.
1935                           Henrik Dam                 -   The deficiency in Vitamin K        -   The vitamin cured
                                                              resulted in the hemorrhage             hemorrhaging of patients
                                                              in chickens.                           with jaundice who lacked
                                                          -   It occurs naturally in                 bile to aid the absorption of
                                                              modified forms in plants               the vitamin and to the cattle
                                                              and produced bacterial                 that eats sweet clover hay
                                                              growth in stored animal                that contained anti-vitamin.
                                                              products.
1929   Essential Fatty Acids   George and Mildred Burr    -   They prepare diets that            -   They discovered that
                                                              were free from fat using               polyunsaturated acids are
                                                              sucrose instead of                     very essential in the diet.
                                                              cornstarch and supplying
                                                              Vitamin A&D by saponifying
                                                              cod liver oil.
                                                          -   As a result, rats fed with
                                                              such diet lose weight and
                                                              lost fur with inflamed tails.
       Proteins and Amino      Osborne and Mendel                                                -   Gliadin isolated from wheat
       Acid                                                                                          supported slower growth
                                                                                                     than what was obtainable
                                                                                                     from casein.
1930                           William Rose & Madelyn     -   They set out to develop            -   It was discovered that one
                               Womack                         amino acid mixtures that               of the active components of
                                                                                                     hydrolysate was isoleucine
                                                                        would support growth in               and the second factor was
                                                                        rats.                                 amino acid known as
                                                                                                              threonine.
                                                                                                          - When it was included in the
                                                                                                              amino acid mix the rats
                                                                                                              grew well and rapidly.
1937       Mineral Elements          Robert McCance and Elsie         - Humans had no ability to          - It was said to be solved by
                                     Widdowson                           excrete iron therefor there          work with dogs using
                                                                         must be a mechanism that             radioactive iron that cast
                                                                         regulated its absorption             their effect after 7 days
                                                                         according to their needs.            when the body iron stores
                                                                                                              had been exhausted as a
                                                                                                              consequence of increased
                                                                                                              synthesis of red cell.
1928       Iodine                    Workers at John Hopkins          - The discreditation on the         - He shows that rabbits fed
                                                                         old idea that goiter was             mainly with cabbage had
                                                                         caused by deficiency of              developed goiters.
                                                                         iodine.                          - His studies on rats showed
                                                                                                              that Brassica plants and
                                                                                                              unprocessed soybeans have
                                                                                                              goitrogenic activity that
                                                                                                              responded to higher intakes
                                                                                                              of iodide.
1930       Fluorine                                                                                       - Fluoride ions was toxic for
                                                                                                              livestock where fluoride-ash
                                                                                                              was scattered.
                                                                                                          - The mottling of the enamel
                                                                                                              of human teeth was
                                                                                                              associated to high fluorine
                                                                                                              content of local water
                                                                                                              supply.
Overall goal of this period: Discovering what was needed to obtain maximum growth rates in young animals with underlying presumption
that this was the good thing.
1917       Diet Restriction and                                                                           - The restriction in the food
           Life span                                                                                          supply of female rats led to
                                                                                                              their living and remaining
                                fertile, with vigorous young
                                to a greater age.
Clive McCay and Lafayette   -   The life of rats particularly
Mendel                          males could be greatly
                                extended by restricting
                                their diet for an initial year
                                or two.